Laser-induced breakdown spectroscopy (LIBS) offers a simple and fast tool for multi-element simultaneous analysis. For optimizing experimental factors in LIBS multi-element simultaneous analysis, an objective function, named “integrated signal-to-background ratio (ISBR)”, is proposed. The coupling influences of the laser energy, measuring time delay, distance between lens and samples, and integration time on the objective function are modeled based on the quadratic regression orthogonal design (QROD). Experimental results indicate that the objective function can contain multiple spectral properties and can provide a standard for the selection of experimental conditions in multi-element analysis. By the multi-factor model built through the QROD, more optimal experimental parameters can be obtained and less experimental numbers are needed than by the single factor experiments.